ROCK Inhibitors against Pancreatic cancer
Stroke medicine has increased the effectiveness of pancreatic cancer treatment
Oleg Lischuk, N+1
A study on mice conducted by Australian, British and American scientists has shown that the administration of the drug fasudil, which is used in the treatment of stroke, increases the effectiveness of chemotherapy and survival in pancreatic cancer. The results of the work are published in the journal Science Translational Medicine.
Pancreatic cancer is a tumor with one of the worst survival rates, even with proper treatment. The most modern therapy of its inoperable forms, including gemcitabine and nab-paclitaxel, prolongs the life of patients by an average of only 8.7 months.
At the same time, the development of malignant neoplasms of the pancreas and their response to medications strongly depends on the microenvironment – connective tissue, blood vessels and immune cells that form a stroma that provides density and blood supply to the tumor tissue. In its formation, as well as the coordinated spread of cancer cells, Rho-linked protein kinases (ROCK) are actively involved, regulating the functions of the actin cell skeleton, and consequently, the shape and movement of cells.
Taking into account these data, the staff of the Garvan Institute of Medical Research in Sydney with colleagues from other research centers tested the effectiveness of the well-known ROCK inhibitor fasudil in pancreatic cancer. This drug, registered in Japan and China, is used to improve blood circulation and prevent cognitive impairment in stroke patients.
Fasudila Molecule (Wikimedia Commons)
Experiments on three-dimensional tissue models have shown that fasudil weakens the tumor stroma, reducing its density and slowing growth. At the next stage of the work, the scientists injected fasudil into mice with implanted human pancreatic neoplasms for three days before starting therapy with gemcitabine and nab-paclitaxel. It also reduced stroma density, slowed down the spread and metastasis of the tumor, as well as increased vascular permeability for chemotherapeutic drugs and improved the response to them both in the primary tumor and in metastases.
As a result, the preparatory therapy with fasudil prolonged the life of mice by 47 percent compared to standard treatment with gemcitabine and nab-paclitaxel. If the drug demonstrates similar efficacy in humans, it will correspond to the prolongation of life from 8.7 to almost 13 months. Such a result seems rather modest, however, given the extremely poor prognosis of patients with pancreatic cancer, this is a serious achievement.
Given that fasudil has already been approved for use in humans, scientists expect to start clinical trials on this indication in a short time. In their opinion, fasudil and another ROCK inhibitor, ripasudil, can increase the effectiveness of chemotherapy and slow down the metastasis of a number of other malignant neoplasms with developed stroma.
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07.04.2017